Sun Chen-Min, Xiong Da-Bo, Yan Yang, Geng Jiang, Liu Min, Yao Xu-Dong
Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai - China.
Int J Biol Markers. 2016 Jul 30;31(3):e286-93. doi: 10.5301/jbm.5000189.
Metabolic alterations in cancer, including bladder cancer, have been addressed in recent years. We aimed to study the role of phosphofructokinase (PFK) in muscle-invasive bladder cancer (MIBC).
By in silico analysis of the bladder cancer data from the Cancer Genome Atlas (TCGA) database using the cBioPortal platform, we studied genetic alteration of genes within the PFK family (PFKL, PFKM, PFKP, PFKFB1, PFKFB2, PFKFB3, and PFKFB4). In vitro studies were carried out using the PFK inhibitor 2,5-anhydro-D-glucitol-6-phosphate.
Genetic alterations of PFK family genes were observed in ~44% of MIBC cases in TCGA. The main alterations were amplification and upregulation. Patients with altered PFK gene status were more likely to have a history of noninvasive bladder cancer. Altered PFK status was not associated with survival or disease relapse. Use of the PFK inhibitor significantly decreased the level of glycolysis and inhibited the growth and invasion of bladder cancer cells.
PFKs were critical genes in charge of glycolysis and were upregulated in bladder cancer. Targeting this pathway could inhibit cell growth in bladder cancer.
近年来，包括膀胱癌在内的癌症代谢改变已得到研究。我们旨在研究磷酸果糖激酶（PFK）在肌层浸润性膀胱癌（MIBC）中的作用。
通过使用cBioPortal平台对癌症基因组图谱（TCGA）数据库中的膀胱癌数据进行计算机分析，我们研究了PFK家族（PFKL、PFKM、PFKP、PFKFB1、PFKFB2、PFKFB3和PFKFB4）内基因的遗传改变。使用PFK抑制剂2,5-脱水-D-葡萄糖醇-6-磷酸进行体外研究。
在TCGA中约44%的MIBC病例中观察到PFK家族基因的遗传改变。主要改变是扩增和上调。PFK基因状态改变的患者更有可能有非浸润性膀胱癌病史。PFK状态改变与生存或疾病复发无关。使用PFK抑制剂显著降低了糖酵解水平，并抑制了膀胱癌细胞的生长和侵袭。
PFK是负责糖酵解的关键基因，在膀胱癌中上调。靶向该途径可抑制膀胱癌中的细胞生长。
